Natural combination hormone replacement formulations and therapies
View Patent ↗Estrogen and progesterone replacement therapies are provided herein. Among others, the following formulations are provided herein: solubilized estradiol without progesterone; micronized progesterone without estradiol; micronized progesterone with partially solubilized progesterone; solubilized estradiol with micronized progesterone; solubilized estradiol with micronized progesterone in combination with partially solubilized progesterone; and solubilized estradiol with solubilized progesterone.
1. A method of treating menopause-related symptoms comprising administering once daily an effective amount of a pharmaceutical composition to a subject in need thereof, the pharmaceutical composition comprising:
about 50 mg progesterone;
about 0.50 mg estradiol or about 0.52 mg estradiol hemihydrate, wherein at least about 90% of the estradiol or the estradiol hemihydrate is solubilized;
about 97.98 mg of a solubilizing agent comprising monoglycerides and diglycerides of caprylic acid and capric acid (CAPMUL MCM); and
about 1.50 mg of at least one of lauroyl macrogol-32 glycerides EP, lauroyl polyoxyl-32 glycerides NF, or lauroyl polyoxylglycerides (GELUCIRE 44/14);
wherein the estradiol or the estradiol hemihydrate, and the progesterone are uniformly dispersed in the solubilizing agent.
2. The method of claim 1 , wherein the pharmaceutical composition is administered as a continuous-combined therapy regimen.
3. The method of claim 1 , wherein the pharmaceutical composition is administered as a sequentially-combined therapy regimen.
4. A method of treating a symptom of menopause comprising administering an effective amount of a pharmaceutical composition comprising:
0.50 mg estradiol or about 0.52 mg estradiol hemihydrate, wherein the estradiol or estradiol hemihydrate is about 90% solubilized in the solubilizing agent;
50 mg progesterone; and
a solubilizing agent;
wherein the estradiol or the estradiol hemihydrate, and the progesterone are uniformly dispersed in the solubilizing agent; and
wherein the pharmaceutical composition is administered once daily for the treatment of symptoms associated with menopause.
5. The method of claim 4 , wherein the pharmaceutical composition is administered as a continuous-combined therapy regimen.
6. The method of claim 4 , wherein the pharmaceutical composition is administered as a sequentially-combined therapy regimen.
7. The method of claim 4 , wherein the solubilizing agent is selected from at least one of monoglycerides, diglycerides, triglycerides, and combinations thereof, wherein the monoglycerides, diglycerides, and triglycerides are predominantly of C6-C12 fatty acid chain lengths.
8. The method of claim 7 , wherein the monoglycerides, diglycerides, and triglycerides are >50% C6-C12 fatty acid chain lengths.
9. A method of treating a menopause-related symptom comprising administering once daily an effective amount of a pharmaceutical composition comprising:
a solubilizing agent;
0.50 mg estradiol or about 0.52 mg estradiol hemihydrate, wherein the estradiol or estradiol hemihydrate is at least about 90% solubilized in the solubilizing agent; and
50 mg progesterone;
wherein the solubilizing agent comprises an oil that is predominantly a C6-C12 oil; and
wherein the estradiol or the estradiol hemihydrate, and the progesterone are uniformly dispersed in the solubilizing agent.
10. The method of claim 9 , wherein the C6-C12 oil comprises C6-C12 monoglycerides and diglycerides.
11. The method of claim 10 , wherein the monoglycerides and diglycerides contain an ester of caprylic acid (C8) and capric acid (C10).
12. A method of treating vasomotor symptoms in a woman comprising administering once daily an effective amount of a pharmaceutical composition comprising:
a solubilizing agent;
0.50 mg estradiol or about 0.52 mg estradiol hemihydrate, wherein the estradiol or estradiol hemihydrate is at least about 90% solubilized in the solubilizing agent; and
50 mg progesterone;
wherein the solubilizing agent comprises an oil that is predominantly a saturated C6-C12 oil; and
wherein the estradiol or the estradiol hemihydrate, and the progesterone are uniformly dispersed in the solubilizing agent.
13. The method of claim 12 , wherein the C6-C12 oil comprises a glyceride of at least one C6-C12 fatty acid.
14. The method of claim 12 , wherein the C6-12 oil predominantly contain an ester of caprylic acid (C8) and capric acid (C10).